Predilution sets for distributing antigens

ABSTRACT

A method for delivering allergens to a pharmacist in a pre-diluted kit form, comprising providing a bulk container of base concentrate antigen containing at least one antigen at a predetermined concentrated level, creating a sequential and more diluted sequence of antigens, providing a plurality of end-use sealable containers that can receive a finite end amount of diluted antigens, dispensing from each of sequential bulk containers a finite end amount of diluted antigens into one of the plurality of end-use sealable containers, wherein the end-use seal containers filled from each of the sequential bulk containers comprises a group of end-use sealable containers associated with each of the sequential bulk containers, sealing each of the end-use containers after diluted antigens are disposed therein, and disposing a select number of the sealed end-use sealable containers from each of the groups of end-use sealable containers into a container comprising a kit.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a Continuation of U.S. application Ser. No.16/531,576, filed Aug. 5, 2019, entitled PREDILUTION SETS FORDISTRIBUTING ANTIGENS. U.S. application Ser. No. 16/531,576 is aContinuation of U.S. application Ser. No. 15/183,719, filed Jun. 15,2016, issued as U.S. Pat. No. 10,369,215 on Aug. 6, 2019, and entitledPREDILUTION SETS FOR DISTRIBUTING ANTIGENS. U.S. application Ser. No.15/183,719 is a Continuation-In-Part of U.S. application Ser. No.15/171,920, filed on Jun. 2, 2016, entitled METHOD FOR MANAGINGREIMBURSEMENTS FOR PREVIOUSLY NON DATABASE ALLERGENS. U.S. applicationSer. No. 15/171,920 claims the benefit of U.S. Provisional ApplicationNo. 62/169,785, filed on Jun. 2, 2015, and entitled METHOD FOR MANAGINGREIMBURSEMENTS FOR PREVIOUSLY NON DATABASE ALLERGENS, and of U.S.Provisional Application No. 62/169,787, filed on Jun. 2, 2015, entitledMETHOD FOR REPURPOSING NDC CODES IN A PHARMACEUTICAL DATABASE FORALLERGENS. U.S. application Ser. No. 15/183,719 claims the benefit ofU.S. Provisional Application No. 62/180,003, filed on Jun. 15, 2015,entitled USE OF AUTOINJECTOR FOR DISTRIBUTING ANTIGENS TO THE PUBLIC,and of U.S. Provisional Application No. 62/176,000, filed on Jun. 15,2015, entitled PREDILUTION SETS FOR DISTRIBUTING ANTIGENS. U.S.application Ser. No. 15/183,719 also claims the benefit of U.S.Provisional Application No. 62/349,626, filed on Jun. 13, 2016, entitledMETHOD AND APPARATUS FOR COMPLETING PRESCRIPTION FOR ALLERGEN COCKTAILWITH PATCH. U.S. application Ser. Nos. 16/531,576, 15/183,719,15/171,920 and U.S. Provisional Application Nos. 62/169,785, 62/169,787,62/180,003, 62/176,000 and 62/349,626 are incorporated by referenceherein in their entirety.

This application is related to co-pending U.S. patent application Ser.No. 15/183,721, filed on Jun. 15, 2016, and entitled USE OF AUTOINJECTORFOR DISTRIBUTING ANTIGENS TO THE PUBLIC, which is incorporated byreference herein in its entirety.

TECHNICAL FIELD

That this application is generally related to the delivery ofimmunomodulators to a patient.

BACKGROUND

Immunotherapy (IT) is recognized as one of the most curative treatmentfor allergies. By exposing the immune system to slowly increasingconcentrations of immunomodulators such as an allergen or antigen, itwill eventually stabilize and regain control the portion that ishypersensitive to the allergen or antigen. In general, immunotherapy isthe “treatment of disease by inducing, enhancing, or suppressing animmune response.” Immunotherapies designed to elicit or amplify animmune response are classified as activation immunotherapies, whileimmunotherapies that reduce or suppress are classified as suppressionimmunotherapies. The active agents of immunotherapy are collectivelycalled immunomodulators. They are a diverse array of recombinant,synthetic and natural preparations, often cytokines.

Immunotherapy involved in the treatment of allergies is a type ofsuppression immunotherapy, often termed desensitization orhypo-sensitization. This is compared with allergy treatments such asantihistamines or corticosteroids which treat only the symptoms ofallergic disease. Immunotherapy is the only available treatment that canmodify the natural course of the allergies, by reducing sensitivity tothe immunomodulators such as antigens or allergens. An antigen and anallergen can both cause one's immune system to respond. An allergen isan antigen, but not all antigens are allergens. An antigen is anysubstance that is capable of causing one's immune system to produceantibodies. They are typically organic, or living, produced proteins. Anallergen is any antigen that causes an allergic reaction. A non-allergenantigen could be a bacteria, virus, parasite, or fungus that causes aninfection. This could also be something else that causes antibody immunesystem response, like toxins, chemicals, tissue cells involved intransplants or blood cells from a blood transfusion. An allergen is anenvironmentally produced substance that causes an allergic reaction,although the substance may not be harmful. Allergens cause no reactionsin some individuals, while possibly causing a hypersensitive reaction inothers. Common allergens include such things as pollen, plants, smoke,feathers, perfumes, dust mites, toxic mold, food, drugs, animal dander,and insect bites and stings.

The exact mechanisms of how IT works are not fully understood, but theyinvolve shifting a patient's immune response from a predominantly“allergic” T-lymphocyte response to a “non-allergic” T-lymphocyteresponse.

Current accepted processes for performing allergy immunotherapy includeinjecting immunomodulator matter in the form of antigen material intopatient subjects. This is referred to as subcutaneous immunotherapy(SCIT), requiring a patient to visit a doctor's office for weeklyinjections. It's is very expensive and time-consuming. A secondtechnique, sublingual immunotherapy (SLIT), involves the application ofallergy extracts (antigens), and allergens placed into a pill form andswallowed by the patient or disposed in “allergy drops” which are placedunder the tongue for the allergens/antigens to be absorbed into the oralmucosa. Transdermal patches may have been used without much success andmostly were used for patch testing to see if a patient reacts to variouschemicals or allergens.

Of the people who start traditional subcutaneous injected immunotherapy(SCIT), 90% fail to complete their therapy due to needle fatigue and notbeing able to see a doctor in their office once or more per week forseveral years. Further, doctors charge for every one of those visits.Further, doctors trained to give injections for allergy are concentratedin high population and upper middle class places. People in rural areasand people who do not live in upper middle class areas cannot get to anallergist for shots. Consider an inner city kid having to ride publictransportation and pay a high copay just to get a high risk injection ifan alternative therapy were available!

Allergies are also linked to depression and suicide and are among thetop ten reasons for missed work and lost productivity. Lastly, allergiesand asthma result in billions of dollars in lost productivity andhealthcare costs among the 90% of allergy patients that either never getimmunotherapy or fail immunotherapy delivered under its currentadministration methods.

Currently, allergens are not readily reimbursed when received from apharmacist for the simple reason that the National Drug Code (NDC) codeis not included in the database to which the pharmacist has access.Without an NDC code in the database, the pharmacist cannot access thatinformation. By not being able to access information, the pharmacistcannot interface with a benefits provider for reimbursements nor canthey have access to the Average Wholesale Price (AWP), which is thebenchmark that has been used for many years for pricing andreimbursement of prescription drugs for both government and privatepayers. Initially, this AWP was intended to represent the average pricethat wholesalers used to sell medications to providers, such asphysicians, pharmacies, and other customers. However, the AWP is not atrue representation of actual market prices for either generic or branddrug products. AWP has often been compared to the “list price” or“sticker price”, meaning it is an elevated drug price that is rarelywhat is actually paid. AWP is not a government-regulated figure, doesnot include buyer volume discounts or rebates often involved inprescription drug sales, and is subject to fraudulent manipulation bymanufacturers or even wholesalers. As such, the AWP, while usedthroughout the industry, is a controversial pricing benchmark.

The AWP may be determined by several different methods. The drugmanufacturer may report the AWP to the individual publisher of drugpricing data, such as Medi-Span. The AWP may also be calculated by thepublisher based upon a mark-up specified by the manufacturer that isapplied to the wholesale acquisition cost (WAC) or direct price (DIRP).The WAC is the manufacturer's list price of the drug when sold to thewholesaler, while the DIRP is the manufacturer's list price when sold tonon-wholesalers. Typically a 20% mark-up is applied to themanufacturer-supplied WAC or DIRP, which results in the AWP figure.

The publishers then in turn sell these published AWPs to government,private insurance, and other buyers of prescription drugs, who use thesedata tables to determine reimbursement and retail prices. Because AWP isa component of the formulas used to determine reimbursement, elevatedAWP numbers can drastically increase the dollar amount that government,private insurance programs, and consumers with coinsurance must pay.

Pharmacies typically buy drugs from a wholesaler and then sell them tothe public. Many patients have coinsurance or copayments, where theyonly pay for a portion of their prescription cost. The insurance companythen pays the rest of the cost (the reimbursement) to the pharmacy.Insurance companies include prescription benefit manager (PBM), healthmaintenance organization (HMO) or government programs, such as Medicaidor Medicare Part B or D. In addition, the pharmacy receives a dispensingfee for filling the prescription. Fees are, for example, set between $3to $5 per prescription, but may vary by state.

Reimbursements are based on AWPs. However, pharmacies purchase drugsbased on the WAC. The difference between the WAC (what the pharmacyactually paid for the drug) and the reimbursement from insurance (basedon AWP) is known as the spread, and equates to the profit that thepharmacy receives. Market pricing on brand drugs tend to be about 16.6percent less than the AWP.

However, the relation of AWP to generic pricing is not clear. Oldergenerics tend to have a large spread between the AWP and WAC, which inturn gives a large spread, and higher profit margins for the pharmacy orother provider of the drug. Many payers, such as PBMS or HMOs, willdetermine a maximum allowable cost (MAC) pricing on generics to avoidbeing overcharged. Newer generic products, compared to older generics,may not have as favorable of a spread, thus the need for MAC.

Collusion between AWP publishers and wholesalers to artificially inflatethe AWP, and in turn increase the spread, has led to court cases in theU.S. In these cases, it was alleged that increasing the spread benefitedthe wholesaler because customers (pharmacies and large institutions)were more likely to buy from them than a competing wholesaler where thespread was not as desirable. The publisher of AWPs profited becausepharmacies were more likely to buy the pricing lists from the publisherthat noted the higher AWPs used in calculating the spread, than to buythem from other publishers with lower AWPs. Due to this pricing fraud,many payers, including government payers, are no longer using AWP forpricing, and are switching to other more transparent pricing benchmarks,such as WAC or AMP (average manufacturers price). However, AWP may stillbe found in use in the U.S. because it has been the standard fordecades.

However, in order for a pharmacist to access the AWP and to be able tointerface with benefits providers, the product associated with an NDCmust be in the database. Currently, allergens are on item that does notexist in the database.

SUMMARY

In one embodiment, a method for delivering allergens to a pharmacist ina pre-diluted kit form is provided. The method comprises providing abulk container of base concentrate antigen containing at least oneantigen at a predetermined concentrated level, providing a plurality ofsequential bulk containers each containing a fixed amount of a carriersolution for diluting antigens. The method further comprises creating asequential and more diluted sequence of antigens by the steps of a)dispensing from the bowl container a fixed amount of the baseconcentrate antigen containing at least one the antigen at thepredetermined concentrated level to a first of the sequential bulkcontainers for being diluted in the carrier contained therein, b)dispensing a fixed amount of the contents of the first of the sequentialbulk containers to a next of the sequential bulk containers for beingdiluted in the carrier contained therein, and c) sequentially repeatingstep b dispensing a fixed amount of the contents of a previous one ofthe sequential bulk containers to the next of the sequential bulkcontainers for being diluted in the carrier contained therein until thelast of the sequential bulk containers has contents dispense thereinfrom the previous of the sequential bulk containers. The method furthercomprises providing a plurality of end-use sealable containers that canreceive a finite end amount of diluted antigens, dispensing from each ofthe sequential bulk containers a finite end amount of diluted antigensinto one of the plurality of end-use sealable containers, where in theend-use seal containers filled from each of the sequential bulkcontainers comprises a group of end-use sealable containers associatedwith each of the sequential bulk containers, sealing each of the end-usecontainers after diluted antigens are disposed therein, and disposing aselect number of the sealed end-use sealable containers from each of thegroups of end-use sealable containers into a container comprising a kitto provide a plurality of kits for dispensing to a patient.

BRIEF DESCRIPTION OF THE DRAWINGS

For a more complete understanding, reference is now made to thefollowing description taken in conjunction with the accompanyingDrawings in which:

FIG. 1 illustrates a diagrammatic view of a dilution sequence ofdiluting a concentrated antigen extract;

FIG. 2 illustrates a diagrammatic view of a production line for fillingdistribution bottles;

FIG. 3 illustrates a flow chart for the dilution process;

FIG. 4 illustrates a flow chart for the dispensing process;

FIG. 5 illustrates a diagrammatic view of a color-coded box withdifferent diluted levels of allergens;

FIG. 6 illustrates a cross-sectional view of a low dose bottle;

FIG. 7 illustrates a process flow for diluting an antigen extract;

FIG. 8 illustrates a process flow for the overall distribution chain;

FIG. 9 illustrates a process flow for multiple extracts;

FIG. 10 illustrates an alternate embodiment of FIG. 9;

FIG. 11 illustrates a flowchart for one example of processing aphysician script;

FIG. 12 illustrates a diagrammatic view of a table in a relationaldatabase relating distributed doses back to NDC-bearing dose;

FIG. 12A illustrates a diagrammatic view of a table showing the dilutionprocedure;

FIG. 13 illustrates a second example of that illustrated in FIG. 11;

FIG. 14 illustrates a diagrammatic view of processing of a scriptreceived from a physician at a pharmacist to compound a patient-specificdosage;

FIG. 15 illustrates an alternate embodiment of that illustrated in FIG.14;

FIG. 16A illustrates a diagrammatic view of a process of filling ascript received from a position and FIG. 16B illustrates a tableassociated with such process;

FIG. 17 illustrates an overall process flow illustrating the prick test,the script flowing through to the final patient does; and

FIG. 18A illustrates a flowchart for parsing an antigen having a basedose with more than the prescribed antigens and FIG. 18B illustrates atable associated with the parsing operation.

DETAILED DESCRIPTION

Referring now to the drawings, wherein like reference numbers are usedherein to designate like elements throughout, the various views andembodiments of a method for delivering immunomodulators to a patient forthe treatment of allergies in pre-dilution sets are illustrated anddescribed, and other possible embodiments are described. The figures arenot necessarily drawn to scale, and in some instances the drawings havebeen exaggerated and/or simplified in places for illustrative purposesonly. One of ordinary skill in the art will appreciate the many possibleapplications and variations based on the following examples of possibleembodiments.

Referring now to FIG. 1, there is illustrated a depiction of a typicaltechnique for diluting immunomodulators such as antigens, as oneexample. Preparation of a diluted antigen is performed first byreceiving a bottle of extract concentrates from an approved vendor.These are formulated in a given weight/volume (w/v) format with a givenantigen associated therewith. For typical antigens such as thoseassociated with the cat antigen, these are relatively well controlled.Typically, a vendor will provide an extract for a single antigen orallergen. Allergens such as pollen and the such are not as wellcontrolled due to the technique for collecting such. In any event, thereare typically very few approved vendors for these extracts and allergisttypically receives these vendor provided concentrates in a sufficientquantity to make the necessary diluted solution.

Allergen extract is typically comprised of a non-allergenic material, anon-allergenic protein and an allergenic protein. The extractionsolutions can be aqueous containing saline and phenol which could be aglycerinated solution. The allergen is added, the units of measure aresometimes referred to as “AU” for “allergy units,” typically used formites. These are referred to as “AU/mL.” For such things as grass andcats, the term “BAU” is used for “bioequivalent units.” For otherallergens, the terminology is, for example, 1:20 w/v, which stands for 1g source material per 20 mL of fluid. The relationship between BAU and1:20 w/v depends upon the extract. In any event, there is a definedamount of extract contained within the concentrate.

When concentrated extracts are formulated by an authorized vendor, theyare typically provided in standardized versions and non-standardizedversions. In standardized versions, they typically are provided in a 50%glycerin dilutant. They can either be a single allergen extract or theycan be a mix. For example, one can obtain a “9 Southern Grass Mix(concentrate)” which contains equal parts of: 2 Bermuda at 10,000BAU/mL, P27 7 Grass at 100,000 BAU/mL, and 15 Johnson at 1:20 w/v. Fornon-standardized extracts, these are typically provided in either aglycerin dilutant or an aqueous dilutant such as saline. They can be asingle extract or a mix. Thus, whenever a concentrated extract isreferred to hereinbelow, this refers to a formulation that is providedby an authorized vendor that can be diluted in accordance with theprocesses described hereinbelow. These are typically provided in the 50mL bottles with a needle compatible.

Referring back to FIG. 1, the extract concentrate is disposed in abottle 102. This is a sterile concentrate that has an injectionstoppered top 104. There are provided a plurality of five 5 mL sterileinjection stoppered bottles 106, 108, 110, 112 and 114, although therecould be more and the bottles or containers could be larger than 5 mL.Each of these bottles has disposed therein a defined amount of dilutant,depending upon what the final dilutant is required to be. Typically, theamount of dilutant is 4.5 mL. The procedure is to, first, extract adefined amount of the concentrated extract from the bottle 102 anddispose it in the bottle 106. This is facilitated by the sterilehypodermic that is inserted through the stopper at the top of the bottle102 to extract concentrate and then the hypodermic is inserted to thestopper in the bottle 106 to inject extract from bottle 102 into bottle106. Typically, the concentration in the concentrated extract bottle 102is 1:20 w/v. This will result in a dilution of 1:10 in bottle 106. Ifthe amount injected is 0.45 mL. Then, 0.45 mL of the diluted solutionfrom bottle 106 is extracted and inserted into bottle 108, resulting ina 1:100 dilution of the original concentrate in model 108. The processis repeated up to the bottle 114 to provide a solution that is at adilution of 1:100,000 of the original concentrate. This is aconventional way to provide a selected dilution of the original antigen.However, it should be understood that any concentration level can beprovided from one bottle to the next. Purpose of using the sequentialbottles is to allow an achievable portion of one bottle to bedistributed to the next bottle, rather than trying to extract a verysmall amount of the initial concentrated extract. Typically, anallergist will then extract from the desired dilution an amount of thediluted antigen for injection percutaneously. Typically, desensitizationis achieved by using the most diluted antigen level initially andsequentially moving up to a higher concentration level over time 1.

Illustrated in FIG. 1 are three hypodermic needles, one selecting a“dose” from bottle 114, and labeled hypodermic 116, a second hypodermicneedle 118 for retrieving a dose from bottle 112, a third hypodermicneedle 120 for extracting a dose from bottle 110. Each of the hypodermicneedles 116, 118 and 120 will contain a different diluted dose. Thesewould typically be separate needles in the event that the allergist ormedical professional is injecting a patient. For other purposes, theycould be the same needle, depending upon the dose or concentrationrequired. A “dose” is defined by the amount of all the diluted productthat would be required for the desired immunotherapy. This is defined bythe medical professional. If, for example, bottle 112 were utilized, itmay be that 1 mL of diluted solution constituted a “dose.” It could bethat less than 1 mL constituted a “dose.”

In general, the typical distribution chain requires that the allergistor other medical professional purchase the base concentrate and thenperform the dilution process. However, this procedure typically requiresbreaking the seal on the base concentrate bottle and then inserting aneedle into the base concentrate bottle for the first dilution step.This occurs multiple times. Thus, multiple needles, each being sterile,can be used one time or, more commonly, a single needle is utilized inassociation with the base concentrate bottle, with the assumption that,since it does not involve insertion into human flesh, it is stillsterile. In any event, this needle must penetrate the rubber stopperseal on the base concentrate bottles multiple times. In fact, thesebottles could typically be held upside down and they would leak and,once the seal is broken, there is no sterile cover over the rubberstopper. This is a result of the multiple needle piercings of the rubberstopper. This is also the case with the small 5 mL bottles in that eachhas to be penetrated at least twice in the higher concentrate bottles.Thus, the last bottle that the allergist has would be a 5 mL bottle andthis bottle would already have one piercing of the rubber stopper sealin order to provide the initial dilution level into the carriermaterial, such as saline. Thereafter, a patient might be able to receive5 or 10 doses from that particular bottle, requiring 5 or 10 morepiercings of the rubber stopper. During this time, of course, there isno seal over the rubber stopper.

In order to solve this problem, a process is provided whereby theconcentrate bottles are produced from a sterile environment containerwhich Artie has the dilutant provided thereto. This is illustrated inFIG. 2. In this embodiment, a large bottle of base concentrate 202 isprovided at a first concentration. This is then metered into a firstdilutant reservoir 204 via a tube 206 and a metering valve 208. Thefirst dilutant container 204 has contained therein a carrier liquid 210which can be, as described herein below, any of a number of materials,such as saline, glycol and the such. Typically, this depends upon thebase carrier material associated with the concentrate 202. By knowingthe volume of the material to 10 within the reservoir 204 prior tometering therein of the concentrate 202 with the metering valve 208, avery accurate amount of concentrate 202 can be dispensed within thereservoir 204. This metering valve 208 can be controlled to such a levelthat a very fine and controlled concentrated level can be defined. Atthis point in the process, the concentrate 202 defines a “batch”material that, for some allergens, is important. For example, if theallergen was related to pollen or the such, this can vary depending uponthe year, the production harvest, the quality of harvest, etc. Bydefining a batch, and controlling the quality and the concentrationlevel at each step in the dilution level, a very controlled dilutionlevel can be provided for that particular batch.

Once the concentrated level or dilution level in the bottle has beendefined, this is then utilized to provide a controlled amount of dilutedallergen to a second dilution bottle 216 through a metering valve 218.This is repeated for multiple bottles down the line to a last bottle220. Thus, there are then provided a plurality of larger vessels withcontrolled dilution levels at each diluted stage in a sterileenvironment. Each of these bottles 204, 216 and 220 has associatedtherewith a control metering valve 222 and a dispensing nozzle 224 thatis operable to dispense diluted allergen material into a receptacle.This metering valve 222 and associated nozzle 224 are all approved tointerface with an approved bottle.

In the dispensing process, there are provided for each dilution stage aplurality of bottles 230. Each of these bottles has a shape and openingthat is approved to be interfaced with the nozzle. Each is passed by thenozzle and an exact amount of diluted material, the allergen, dispensetherein. Thereafter, each bottle 230 is then subjected to a Procedurewhich inserts the rubber stopper and the seal there over. The result isa bottle with a defined dosage amount at a defined concentration levelfor a known batch of allergen, all of which is a sterile environment.The allergist or medical professional need only then remove this seal,insert the needle through the rubber stopper and extract the appropriateamount of diluted allergen. This particular bottle 230 is designed to bea single dose. Thus, the actual amount of material disposed within thebottle will be approximately 1 mL. Typically, the bottles are 5 mLbottles. In this situation, that 5 mL bottle can be modified to maintainthe same size but only provide for a single 1 mL dose. This will bedescribed hereinbelow.

Referring now to FIG. 3, there is illustrated a flowchart for theoverall dilution process, which is initiated at a block 302. The processflows to a block 304 to provide the base concentrate. As notedhereinabove, the base concentrate is typically associated with a fixedbatch so that it is a well-controlled product and this is a sterilebottle within a sterile environment and the size can be larger thantypically distributed to an allergist. The process flows to a block 306wherein the various dilutant containers are provided with a sterilizedbase liquid such a saline or glycol, depending upon intended final use.The process then flows to block 308 wherein a metered amount of dilutantis passed from the base concentrate vessel to the first dilutantcontainer. The process then flows to a block 310 wherein a meteredamount of diluted allergen is transferred from the previous bottle tothe next bottle until the last bottle is complete, which is determinedat a decision block 312. This will then result in multiple vessels ofdiluted allergen at the appropriate diluted level for final dispensing.The program then flows to a block 316.

Referring now to FIG. 4, there is illustrated a flowchart for thedispensing operation, which is initiated at a block 402. The processflows to a block 404 wherein a nozzle is inserted from the selectdilutant container or vessel to the final dispensing bottle, typically asingle dose bottle. The process then flows to a block 406 to meter afinite dose to the end user bottle. Again, this could be a 1 mL dose ina 5 mL bottle or a 1 mL dose in a 1 mL bottle. The process then flows toa block 408 to send the end user bottle to capping, followed by aprocess block 410 to dispose a cap on the bottle, this being a rubberseal to allow insertion of the needle there through, and then to a sealblock 412 to provide a sterile seal over the bottle and then to aterminate block 416.

Referring now to FIG. 5, there is illustrated a depiction of a deliverycontainer for the final allergen in the bottles 230. The bottles wouldtypically be controlled such that they would have, for example, a verydistinctive color associated with each diluted level. The highestconcentration bottle would be a bottle that would have to be carefullydispensed to a patient, as, if not adequately desensitized to theallergen, this could result in anaphylactic shock to the patient. Thus,it is important that the correct dose at the correct dilution level isadministered at a particular time. This color coding process for anytype of identification process clearly presents to the medicalprofessional some clear indication of the concentrated level ofallergen. Typically, these allergens will be provided in a kit form. Forexample, it may be that a patient would require the lowest concentratelevel of the allergen three times per week for two weeks, followed bythe next concentrated level of allergen two times per week for one week,etc. Thus, the various diluted levels of concentrate would be providedin single-dose bottles to, for example, a pharmacy, which would dispensethe particular dosages. The first thing is that they would be from acommon batch and they would be provided to the patient in theappropriate presentation. For example, the patient might receive a firstbox of six bottles 230 at the lowest concentrate level for the first twoweeks. The pharmacist then would provide the second part of theprescription for the second level in the form of two bottles ofconcentrate at the next level, this all being color-coded. The box mightbe color-coded, as well as the bottles. Again, each of these bottleswould be a single dose. Since they are all single-dose and containedwithin sterile bottles, the shelf life is considerably longer.

Referring now to FIG. 6, there is illustrated a cross-section of atypical bottle that would be involved with respect to providing a singledose of 1 mL in a larger standard 5 mL bottle. A 5 mL bottle isrepresented by a bottle 602. This bottle 602 has an opening 604 that isprovided for the 5 mL bottle. An insert 606 is provided for fillingspace within the bottle. This can be any type of plastic insert, etc. Asmaller insert bottle 608 is disposed within the insert 606 to providean elongated interior 620 which has a volume slightly in excess of 1 mL,such that a 1 mL dose can be disposed therein. This elongated interioris covered with a rubber stopper 622 such that a needle 624 can bedisposed there through and be able to extract 1 mL of diluted antigen.If not for the elongated opening 620 facilitated by the insert 606 inthe bottle 608, the 1 mL of diluted antigen would be disposed at a lowerlevel and would be more difficult to extract.

Referring now to FIG. 7, there is illustrated a process flow for theembodiment of FIG. 1. This is initiated at a process block 702 and thenproceeds to block 704 wherein a certain amount of concentrated extractis received from a vendor, this being a qualified or authorized vendorfor the extract. This is typically at a predetermined concentrate levelof, for example, 1:20 m/v. The process then flows to a block 708 whereina defined quantity of, for example, 0.45 mL is transferred to a 5 mLbottle which already has a quantity of 4.5 mL buffered saline solutiondisposed therein. The process then flows to a block 710 to determine ifthis was the last dilution step needed, as described hereinabove,depending upon what level of dilution is necessary. If, for example, bysteps of dilution are required for a particular patient, and all fivesteps would be processed. However, it is not necessary to do all fivesteps if an intermediate dilution is required. This essentiallycustomizes the overall operation for a particular patient. Further, theindustry is so regulated such that only 5 mL bottles can be utilized forthis dilution process. Thus, it will only be a maximum of 5 mL ofdiluted material available at any step prior to proceeding to the nextstep. Thus, if all 5 mL are required, then the next step is not desiredor useful. If it is not the last dilution step, the process flows to ablock 712 to extract 0.45 mL of diluted antigen from the current 5 mLbottle and then flows back to the input of the process block 708 afterincrementing the bottle count at a block 714. This continues until thelast dilution, at which time the process flows from the block 710 to aterminate block 716. Again, any type of carrier could be utilized andbottles larger than 5 mL could in fact be utilized. This all dependsupon the number of “doses” at a particular diluted level that arerequired by the physician right the initial script or prescription.

Referring now to FIG. 8, there is illustrated in overall flow of theoperation of moving concentrated antigen from a vendor to an end uservia a pharmacist. As noted hereinabove, the liquid antigen in aconcentrated extract at the base concentrate level that has associatedthere with an NDC was first received from a vendor that assigned thatNDC, which is basically a combination of a single antigen or antigenssuspended in a sterile agent. This is indicated by a block 802. Theantigen is then diluted by the pharmacist from this extract to a desireddiluted level, as indicated by a process block 804. This is combined ina block 806 with a sterile carrier and containment material, i.e.,sterile saline solution or, even a transdermal cream, for distributionto a patient. This, as described hereinabove, will typically be adefined number of doses of a single diluted antigen or multiple dilutedantigens, wherein a dose is again defined as being a typical dose that amedical professional would administer to a patient in an office visitnecessary to achieve a therapeutic result for which a patient couldadminister to themselves. This is either transferred as a combinedantigen (diluted)/encapsulation product for storage on a shelf, asindicated by a block 812, or it would be transferred to a medicalprofessional for a patient for management and disposition.

Referring now to FIG. 9, there is illustrated a diagrammatic view ofthree different extracts of antigens/allergens 902, 904 and 906. Each ofthese is for a particular antigen or allergen. The first two are forantigens respectively associated with a cat and a dog. The third is foran allergen associated with pollen. They are each diluted in accordancewith the process described hereinabove with respect to FIG. 1. Asillustrated, the antigen extract in bottle 902 is transferred as adiluted level to either an encapsulation material in a container 910 or912, each at a different diluted level. This is similarly the case withrespect to the antigen in bottle 904 and the allergen in 906 wherein thediluted level of the antigen in the bottle 904 is disposed in containers914 and 916 and the diluted level of the allergen in bottle 906 isdisposed in containers 918 and 920. Typically, any extract will be 100%pure with respect to the particular extract. These concentrated extractsare not typically mixed, which is typically a function that the medicalprofessional or compounding pharmacist will perform. This, of course, isa customized mixture for a particular patient, i.e., this is apatient-specific combination as defined by the medical professional inthe script provided to the pharmacist. For storage on the shelf, theoperation of FIG. 9 will be facilitated in order to ensure that thecontainers 910-920 contained only a single antigen. Thus, whentransferring the container to a store, for example, this would be storedon the shelf as a single allergen combination of the base concentratelevel. The antigens/allergens 902, 904, and 906 may also have been partof the kit described with respect to FIG. 5. In that case, thepharmacist would still create a customized mix for the patient. Forexample, if the pharmacist received a kit for cat, dog, and pollen, anda prescription for a particular dosage of each (1 mL for example), thepharmacist would create a new bottle filled with one dose ofantigen/allergen for cat, one dose for dog, and one dose for pollen. Thedosage level (1 mL) may then be tracked back to the NDC code for eachantigen/allergen. For example, if 1 mL of cat is associated with an NDCcode having a price of $50 associated therewith, and the same is truefor dog and pollen, then a total cost of $150 may be appropriate,allowing for the pharmacist to be reimbursed for that amount.

Referring now to FIG. 10, there is illustrated an alternate disclosureto that of the embodiment of FIG. 9. In this embodiment, each of theimmunomodulators or antigens at the concentrated levels in the bottles902-906 are diluted in accordance with the process noted hereinabovewherein they are sequentially diluted in the associated 5 mL bottles.However, note that only a maximum of 5 mL can be extracted from a givenbottle at the last dilution level. If, in this example, it is desired todistribute a predefined number of doses to a final carrier 1002 having afixed amount of carrier such as saline disposed therein and each dosewill add to that material provide the final overall dosage or,alternatively, a viscous transdermal cream can be utilized that isinitiated at an original fixed value in grants such that each dose willbe associated with a single gram of that transdermal cream material, andthen the amount of diluted antigen must be adjusted such that singledose is contained within 0.3 mL of the material. Thereafter, if 3 mL ofantigen is extracted from a given bottle, this constitutes 30 doses suchthat a single dose will be associated with a single dose of the finalencapsulation material. In this example, from each of the last dilutionbottles for each of the concentrate bottles 902-904, 3 mL is extractedand inserted within the container 1002 containing prescribed level ofcarrier material, be that saline solution or a transdermal cream. Thus,for each milliliter of saline solution, for example, or each gram oftransdermal cream material, there will be a single dose of theparticular antigen associated there with. Thus, the carrier material inthe container 1002 now acts as a consolidator of all of the antigens fora cocktail.

Referring now to FIG. 11, there is illustrated a flowchart depicting oneexample of the generation of a script for a single antigen and fillingof that fiction based on that script and getting reimbursed therefor.This is initiated at a block 1102 and then proceeds to a block 1104 inorder to prepare the physician script for a single antigen. The programthen flows to a block 1106 in order to define the requirements of themaximum dilution for the initial desensitization. The physician definedat which level the script is written for. For example, the physiciansets forth a regimen. This regimen defines six levels of dilution, eachlevel of dilution are required for a predetermined amount of time. Forexample, the most diluted level might be required to be administered inthree doses per week for three weeks for total of nine doses. The firstscript would require the pharmacist to deliver to the patient a filecontaining nine doses at that diluted level of the at least a singleantigen. The physician could then require the second higher level to beprovided over the course of one week at three doses per week. This mightrequire a second script to be filled by the pharmacist or,alternatively, the pharmacist could fill that script that same time andmaintained that particular vial on the shelf for distribution to thepatient at a later time, all of this depending upon the script providedby the physician. Of course, the physician could require the patient tocome into the office for observation and then write another script. Thiswould be a separate and distinct operation and prescription which wouldbe independently associated with a different set of benefits possibly.

After the dilution level is determined for the initial desensitizationor at any level in the desensitization regimen, the program flows to afunction block 1108 wherein the pharmacist selects concentrate antigenand then goes to the dilution process required order to achieve thedesired diluted level. The program then proceeds to a function block1110 where in the pharmacist enters the NDC code for the baseconcentrate level and the script level. Basically, what the pharmacistdoes is enter the antigen name and the dosage level provided by script.The program then proceeds to a function block 1112 in order to perform alookup in the PBM database for the particular antigen that is associatedwith the script. This lookup does a correlation, as will be describedhereinbelow, to the lowest concentrate level having an NDC for thatparticular antigen. Knowing the dilution level and the procedure, it ispossible to determine what amount of the NDC-carrying concentrate levelfor that particular antigen was utilized and then a reimbursementobtained and four. This is indicated by the function block 1114 and1116. The program then flows to an initial End block 1118.

Referring now to FIG. 12, there is illustrated a table for a singleantigen and the overall crosscorrelation information. This is arelational database. In this table can be seen that there is provided acolumn for the NBC code which is populated for a particular antigen.This indicates the name of the antigen and also information associatedthere with. There is also a dilution procedure for multiple proceduresthat can be associated with administering this particular antigen. Sincethe NBC code associated only with the type of antigen but also theconcentration levels, this will be associated with the dilution level todetermine what the various dilutant levels are in the overall standardprocess. As noted, the base level is indicated by a dilutant level D1 ora base concentrate level there than provide five additional dilutantlevels D2 through D6. Each one of these dilutant level columns hasassociated there with a particular range of dilutant levels. Asindicated by example, there are levels 1 through 3 for each of dilutedlevels, with more possible. Therefore, if the most diluted level, D6were selected and that the procedure required that the dilutant level Z6for the dilutant level column D6 were selected as the N dilutant levelthat was required by the physician in the script provided to thepharmacist, this would be what was put into the PBM system. However,there is no NDC associated with this particular antigen at thisparticular dilutant level. Therefore there must be some crosscorrelationback to column D1 for the base concentrate level, which column has anNDC associated there with. If the final dilutant level was Z6, thiscould be cross correlated back within the same road to the dilutantlevel Z1 of the base concentrate. However, although not shown, therecould actually be multiple roads associated with the dilutant level Z6,one for each dilution procedure. Thus, the crosscorrelation from theaxle in dilutant level back to amount of bass constitute antigenrequired to process through the diluting procedure requires knowledge ofthe diluting procedure. This is illustrated in FIG. 12A, wherein eachcolumn for the dilutant level Z6 has three has such that there areprovided three different amounts of the base extract that would berequired, Z1, Z2′ and Z″. For example, it might be that this requirescorresponding levels of 0.8 mL, 1.0 mL or 1.1 mL for those threedifferent levels in order to accommodate the three different dilutionprocedures S1, S2 and S3. Thus, it is not just a mere crosscorrelationoperation but, rather, and overall knowledge of the process that isrequired in order to determine how much actual product was utilized ofthe original base NDC-carrying antigen. Only when the amount of the baseconcentrate NDC-carrying antigen that is utilized is known can theactual dosage be determined. For reimbursement purposes, it is importantto know whether 0.8 mL, 1.00 mL or 1.1 mL was use of the baseconcentrate NDC-carrying antigen is utilized. Reimbursement iscalculated based upon this. However, all that is necessary for thepharmacist to do is to put in the end product that was generated and theprocedure for coming up with that end product and relate that to theantigen that was utilized.

Referring now to FIG. 13, there is illustrated a flowchart for a secondexample for preparing a script for a cocktail, which is similar to theflowchart of FIG. 11. This is initiated at a block 1302 and thenproceeds to a block 1304 to generate a script for a cocktail which is apatient-specific cocktail based upon a prick test performed. This isunique to that patient for that particular time. The program thenproceeds to a function block 1306 in order to provide in that script alist of the antigens to be placed into the cocktail by the pharmacist,the final dilutant level of each, the dosage and the particular carrier.The program then flows to a function block 1308 in order to select theprocedure that the pharmacist will utilize to provide this final dilutedproduct with the prescribed number of dosages. This might be prescribedby the position or it might be selected by the pharmacist. The programthen flows to a function block 1310 wherein the pharmacist performs thedilution operation and then combines various antigens into the cocktail,at a block 1312. The program then proceeds to a function block 1314wherein the NDC for each antigen is entered into PM database, the doselevel and the procedure. The program then proceeds to a function block1316 to parse the particular antigens at the database, this parsingrequired in order to process each antigen in the database separately, asthere must be a crosscorrelation back to each individual antigen, sinceonly each individual antigen has an NDC associated there with. Theprogram then proceeds to a function block 1318 in order to correlate theantigen back to the lowest concentrate NDC-carrying level, as describedhereinabove with respect to the embodiment of FIGS. 11 and 12 and thento a function block 1320 in order to define the benefits and then to afunction block 1322 in order to end the program, after the cocktail hasbeen distributed to the end user such as the patient or the medicalprofessional.

Referring now to FIG. 14, there is illustrated a process, which issimilar to that described hereinabove, for creating a cocktail fromthree different base concentrate antigens 902, 904 and 906, referringhereinabove to the description with respect to FIG. 9. These are diluteddown in five separate steps to a final dilution level D6. In a firstoperation, there is provided a final vial 1402 that receives the finaldosage from each of the processes for diluting the initial baseconcentrate levels. It may be that each of the final vials D6 each have5 mL contained therein. By containing no carrier material in the finalvial 1402, 3 mL of each of the extract can be placed therein resultingin a vial with 9 mL therein. If the physician prescribed the regimen todeliver a 1 mL dose of this concentrated level III times per week forthree weeks, this would require nine doses and thus 9 mL of thecocktail. This overall process, for example, would require thepharmacist to understand each step of the dilution process to arrive atthe final diluted. Thus, the pharmacist would indicate that there werethree antigens in the final vial 1402 and that they were at theconcentrate level D6/D6/D6. This would be provided to the PDM database.With this information alone, the system at the PDM database can crosscorrelate this back to the exact amount of base concentrate level liesfor each of three base concentrate antigens 902, 904 and 906 utilized.

Alternatively, there is provided a vial 1404 which is the result of adifferent selection of cocktails from the D4 level. This, again, wouldhave the re-antigens in the concentrate level D4/D4/D4. This would againpre-provided to the PDM database which would then, based upon thedilutant level for each of the antigens and the procedure utilized toachieve that dilutant level to relate this back to the antigens utilizedat the NDC-carrying concentrate level. If, for example, this vial 1404resulted in 9 mL of material but the physician only required three dosesof 1 mL each for two weeks, this would only required 6.0 mL. Thepharmacist might only dispense 6 mL out of the 9 mL to the patient orprofessional. Even though he doses distributed or 6.0 mL, this 6 mL offinal product of D4/D4/D4 of Cat/Dog/Pollen antigen has to be relatedback to the original antigen value.

In an alternate embodiment, there is a vial 1406 provided that has beenprovided where in it receives diluted antigens from slightly differentand vials. In this operation, the three antigens are D5/D6/D6 and thisis provided back to the PDM database. Of interest is that all threevials 1402, 1404 and 1406 will each the input to the PDM system withtheir procedure and the result will be that, for this examplespecifically, at the reimbursable be the same, as the starting dilutantwill be identical. This is procedure specific and script specific, withthe cocktail noted as being patient-specific. The antigens/allergens902, 904, and 906 may also have been part of the kit described withrespect to FIG. 5. In that case, the pharmacist would still create acustomized mix for the patient. For example, if the pharmacist receiveda kit for cat, dog, and pollen, and a prescription for a particulardosage of each (1 mL for example), the pharmacist would create a newbottle filled with one dose of antigen/allergen for cat, one dose fordog, and one dose for pollen. The dosage level (1 mL) may then betracked back to the NDC code for each antigen/allergen. For example, if1 mL of cat is associated with an NDC code having a price of $50associated therewith, and the same is true for dog and pollen, then atotal cost of $150 may be appropriate, allowing for the pharmacist to bereimbursed for that amount.

Referring now to FIG. 15, there is illustrated an alternate embodimentwherein each of the base antigens 902, 904 and 906 are subjected to adifferent procedure wherein each of the original starting amounts areinput to a first diluting vial 1502 and are subsequently diluted throughvials 1504, 1506, 1508 and 1510 to a final vial 1512. This is andistributed to the patient. This final vial represents the dilution atthe vial 1510, which is D6/D6/D6. This, along with this is procedure isthen transferred to the PDM database, as indicated by block 1520, whichis then parsed to the specific antigens and into a translator associatedwith each antigen, indicated by a “X” for the crosscorrelationoperation, blocks 1522, 1524 and 1526 associated with the Dog, Cat andPollen antigens which will then define the reimbursement. Eachtranslation block 1522 will be associated with a reimbursement databasefor defined benefits associated with the particular antigen. Of course,it is important to know the amount of antigen that was actually utilizedin the overall procedure which, again, requires knowledge of the finalscript dilutant level of the antigen delivered to the patient andprocedure for obtaining that diluted level.

Referring now to FIG. 16A, there is illustrated a diagrammatic view ofan overall process where in the NDC is associated with an intermediatelevel of dilutant. In this embodiment, the dilutant level D4 isillustrated as having an NDC associated there with, as well as the baseconcentrate level of Thus, it is possible that the reimbursement and bedefined back to this intermediate concentrate level of. This isindicated in a table in FIG. 16B, wherein the table can have associatedwith original diluted levels D4, D5 and D6 crosscorrelationrelationships with respect to the base concentrate level but, in thistable, there are only three diluted levels required, the dilutant levelfor vial D4, the vial D5 and the vial D6. If the concentrate level atthe final vial was X3 based upon the NDC code being at vial D4, all thatwould be required is to do a crosscorrelation back to the dilutant levelrequired from the file D4. This would be for each of the dilutant setwas combined in a vial 1602 from each of the antigens in the script,this indicated as being the antigens A1-N.

Referring now to FIG. 17, there is illustrated a process for mappingprick test to the script. As illustrated, there is provided a diagram ofthe prick test, indicated by a reference numeral 1702. This diagram 1702indicates the locations of the particular allergens that wereadministered to locales on the person of the patient. This diagramillustrates the results with a “P” indicating a positive reaction andthat an “X” indicating a negative reaction. Thus, the “P” indicates asensitivity that must be considered in the script. Of interest is thatthe particular manufacturers of antigens might have a cocktail alreadyexisting in the base concentrate. This is illustrated with the bottomthree test associated with antigens A(n−2), A(n−1) and AN. These are thelast three antigens in the list. Of these, the last two are positive andthe third for the last is negative. However, the script will have toinclude only the last two for the patient-specific script but thepharmacist only has the cocktail of all three available to them. Thus,the script will have a A0, A1, A3, A4 . . . , A(n−1) and AN as theantigens that are required for the desensitization regimen. This will beprovided to the pharmacist which will then select NDC-Kerry antigenbottles A0, A1, A3, A4 . . . , And finally a bottle 1702 containingA(n−2), A(n−1) and AN, wherein only A(n−1) and AN are required in scriptto fill the prescription. This is then processed to provide the finalpatient dosage in the cocktail in the vial 1704.

Referring now to FIG. 18A, there is illustrated a flowchart depictingthe overall parsing operation before the operation of FIG. 17. In thisoperation, if the base NDC has a greater number of antigens than thescript, a decision block 1802 will determine such and flow to a block1804. The program will then flow to a function block 1806 in order todetermine the basis dosage for the script as required by and set forthby the position of the antigens with the particular NDC, even thoughthat NDC IS associated with more than the antigens required by thescript. The program then flows to a function block 1808 in order todetermine the benefits. This is illustrated best with respect to thetable of FIG. 18B. Here, it is illustrated that there are threeprocedures for providing the end dilutant level at the vial D6 for eachof the antigens in the cocktail antigen vial 1702. If a certain amountof antigen is extracted from this particular vial 1702, it will containall three antigens. At a particular concentrate level at the level D6,this will yield the necessary concentrated level of the two antigensdesired even though the third antigen is included. Since the finaldilutant level is known for the two prescribed antigens, they can becross correlated back to the amount of antigen that was actuallyextracted. However, for example, if 3 mL of the extract in vial 1702were extracted, this might represent a particular portion of a 100 mLbottle and, if all three antigens have been prescribed, this would bethe basis for the reimbursement. However, if only to antigens wereprescribed, only two thirds of that prescribed extract would bereimbursed. Thus, by utilizing known script at the known dilutant level,this can be cross correlated back via the standard procedure (orwhatever procedure is utilized) to what was actually utilized of theNDC-carrying base concentrate material to actually derive the finalprescribed and delivered antigen to the patient.

Although the preferred embodiment has been described in detail, itshould be understood that various changes, substitutions and alterationscan be made therein without departing from the spirit and scope of theinvention as defined by the appended claims.

What is claimed is:
 1. A prediluted kit including a range of prediluteddoses of allergens for dispensing to a patient, comprising: a containerhaving a plurality of receiving pockets, each being associated with oneof a plurality of sequential diluted allergen levels all based on a baseconcentrate antigen wherein the base concentrate antigen includes atleast one specific antigen; a plurality of end-use sealable containersof prediluted antigens, wherein the plurality of end-use sealablecontainers are sterile, wherein each one of the plurality of end-usesealable containers is at a defined level and disposed in one of theplurality of receiving pockets, wherein each one of the plurality ofend-use sealable containers is prepackaged as already including the baseconcentrate antigen at a sequential dilution level diluted in accordancewith a predetermined sequential dilution process to provide sequentiallylower dilution levels for use in an allergy desensitization regimenprescribed by a medical professional, and wherein each one of theplurality of end-use sealable containers includes at least one insertoperable to: provide an elongated interior in the end-use sealablecontainer, the elongated interior having a volume corresponding to atleast a dose; and fill space within the end-use sealable container todispose a prediluted antigen at an elevated level in the end-usesealable container for extraction; and an indicator disposed inassociation with each of the plurality of receiving pockets indicatingthe dilution level of the associated one of the end-use sealablecontainers included therein.
 2. The kit of claim 1, wherein each of theplurality of end-use sealable containers includes more than one dilutedantigen.
 3. The kit of claim 1, wherein each of the plurality of end-usesealable containers includes only a single diluted antigen.
 4. The kitof claim 1, wherein a National Drug Code (NDC) of the base concentrateantigen is indicated on the container.
 5. The kit of claim 1, whereinthe indicator comprises a color code, there being a separate color codeassociated with each dilution level and wherein each of the end-usesealable containers associated with each of the dilution levels has acorresponding color code disposed there on.
 6. The kit of claim 1,wherein each of the end-use sealable containers contains only a singledose of diluted allergen, as defined by the medical professional.
 7. Thekit of claim 2, wherein a plurality of National Drug Codes (NDC) isindicated on the container, wherein each of the plurality of NDCs isassociated with a base concentrate antigen of each of the more than onediluted antigen.